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MP13-07 NEXT-GENERATION LIQUID BIOPSIES USING EXTRACELLULAR VESICLE DETECTION BY NANOSCALE FLOW CYTOMETRY

2019· article· en· W2942115245 on OpenAlexaboutno aff
Fabrice Lucien-Matteoni, Janice Gomes, Harmenjit Brar, Matthew R. Lowerison, Mario Cepeda, Vidhu B. Joshi, Yohan Kim, Paras Shah, Stephen E. Pautler, Nicholas Power, Haidong Dong, Stephen A. Boorjian, Bradley C. Leibovich

Bibliographic record

VenueThe Journal of Urology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced Biosensing Techniques and Applications
Canadian institutionsnot available
Fundersnot available
KeywordsFlow cytometryLiquid biopsyMedicineExtracellular vesiclesNanotechnologyCancerArt historyArtCell biologyImmunologyInternal medicineBiology

Abstract

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You have accessJournal of UrologyProstate Cancer: Detection & Screening I (MP13)1 Apr 2019MP13-07 NEXT-GENERATION LIQUID BIOPSIES USING EXTRACELLULAR VESICLE DETECTION BY NANOSCALE FLOW CYTOMETRY Fabrice Lucien-Matteoni*, Janice Gomes, Harmenjit Brar, Matthew Lowerison, Mario Cepeda, Vidhu Joshi, Yohan Kim, Paras Shah, Stephen Pautler, Nicholas Power, Haidong Dong, Stephen Boorjian, and Bradley Leibovich Fabrice Lucien-Matteoni*Fabrice Lucien-Matteoni* More articles by this author , Janice GomesJanice Gomes More articles by this author , Harmenjit BrarHarmenjit Brar More articles by this author , Matthew LowerisonMatthew Lowerison More articles by this author , Mario CepedaMario Cepeda More articles by this author , Vidhu JoshiVidhu Joshi More articles by this author , Yohan KimYohan Kim More articles by this author , Paras ShahParas Shah More articles by this author , Stephen PautlerStephen Pautler More articles by this author , Nicholas PowerNicholas Power More articles by this author , Haidong DongHaidong Dong More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , and Bradley LeibovichBradley Leibovich More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000555220.43463.25AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Next-generation biomarkers are emerging as valuable tools to improve cancer diagnostics, disease stratification and treatment monitoring. Our group has developed an innovative “liquid biopsy” based on enumeration of submicron cell fragments called extracellular vesicles (EVs) that bear tissue and cancer-specific biomarkers. This approach relies on the use of nanoscale flow cytometry (nFC) allowing high-throughput multi-parametric detection and enumeration of particles of events between 100-1000 nm in diameter. Despite the growing interest for developing EV-based blood tests, there is still an unmet need to optimize pre-analytical procedures and analytical parameters. Our team has established the standard operating procedures required for accurate detection of EVs from patient plasmas. METHODS: We utilized the A50-Micro Plus nanoscale flow cytometer (Apogee FlowSystems Inc.) to identify and measure 100-1000nm sized EVs. Silica and polystyrene beads were used to determine resolution limits of the nFC and established optimal acquisition parameters for EV enumeration. Plasmas from healthy volunteers and cancer patients were used to standardize pre-analytical conditions (plasma isolation, storage, handling) and to assess the performance of the nFC. RESULTS: A50-Micro Plus was capable of detecting EVs from 110 to 1000 nm in a linear manner by using light-scatter and fluorescence detection. Platelet-free plasma, storage temperature (-80C), dilution range (1/15-1/60) are critical considerations to ensure integrity and accurate enumeration of EVs. We used the standard operating procedure to enumerate prostate cancer-derived EVs in prostate cancer patients and unveiled a blood signature which identifies patients with clinically significant prostate cancers. CONCLUSIONS: We have established a workflow to develop EV-based liquid biopsies using nanoscale flow cytometry. In prostate cancer, we have identified an EV signature that may enhance selective identification of patients with clinically significant prostate cancer and decrease unnecessary tissue biopsies in individuals with absent or low-risk disease. This technique has the potential to facilitate the development of next-generation peripheral blood tests to allow personalized treatment protocols for patients with urogenital cancers. Source of Funding: Movember Foundation, Mayo Clinic Rochester, MN; London, Canada; Rochester, MN; London, Canada; Rochester, MN© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e179-e179 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fabrice Lucien-Matteoni* More articles by this author Janice Gomes More articles by this author Harmenjit Brar More articles by this author Matthew Lowerison More articles by this author Mario Cepeda More articles by this author Vidhu Joshi More articles by this author Yohan Kim More articles by this author Paras Shah More articles by this author Stephen Pautler More articles by this author Nicholas Power More articles by this author Haidong Dong More articles by this author Stephen Boorjian More articles by this author Bradley Leibovich More articles by this author Expand All Advertisement PDF downloadLoading ...

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.132
Threshold uncertainty score0.278

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.260
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2019
Admission routes1
Has abstractyes

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